A potential new drug for lung cancer has eliminated tumours in 50% of mice in a new study published in the journal Cancer Research. In the animals, the drug also stopped lung cancer tumours from growing and becoming resistant to treatment. The authors of the research, from Imperial College London, are now planning to take the drug into clinical trials, to establish whether it could offer hope to patients with an inoperable form of lung cancer.

One in five people with lung cancer have small cell lung cancer and only three per cent of these people are expected to survive for five years. With this form of lung cancer, tumours spread quickly so it is rarely possible to remove the tumours surgically. Because of this, small cell lung cancer is treated with chemotherapy, with or without additional radiotherapy. Initially, the treatment often appears to work, reducing the size of the tumours. However, the tumours usually grow back rapidly and then become resistant to further treatment.

The researchers behind this study have identified a drug that, in some mice, was able to completely shrink tumours away. In the mouse models, it was also able to stop tumours from growing and it helped other forms of chemotherapy to work more effectively. If the drug proves successful in humans, the researchers hope that it could help patients with this kind of lung cancer to live longer.

In small cell lung cancer, tumours spread quickly because the tumour cells grow and divide faster than normal cells. Previous research carried out by the Imperial team showed that these tumour cells proliferate faster because they are fuelled by a growth hormone called FGF-2. This growth hormone also triggers a survival mechanism in the tumour cells that makes them become resistant to chemotherapy.

In today’s study, the researchers looked at the effect of a drug called PD173074, which blocks the receptor that FGF-2 uses to attach to the tumour cells. The drug stopped cancer cells from proliferating and from becoming resistant to treatment in ‘test-tube’ laboratory models. In one animal model of small cell lung cancer, the drug eliminated tumours in 50% of mice and in a second, similar mouse model, the drug enhanced the effect of standard chemotherapy.

Professor Michael Seckl, corresponding author of the study who heads the Section of Molecular Oncology and Lung Cancer Research at Imperial College London, said: “Lung cancer is the most common cancer killer in the world and over 100 people in the UK are diagnosed with the disease every day. Around one in five of those people will have small cell lung cancer. Although it responds to chemotherapy initially, the tumours soon become resistant to treatment and sadly nearly all people with the disease do not survive.

“We urgently need to develop new treatments for this disease. Our new research in mice suggests that it may be possible to develop the drug PD173074 into a new targeted therapy for small cell lung cancer. We hope to take this drug, or a similar drug that also stops FGF-2 from working, into clinical trials next year to see if it is a successful treatment for lung cancer in humans. An added bonus of this drug is that it could be taken orally, which would make it less invasive than some other forms of cancer therapy,” added Professor Seckl.

The researchers first studied the effect of PD173074 in the lab, on cells taken from human tumours. The drug stopped cells from proliferating and prevented FGF-2 from triggering their survival mechanism, so the cells could be killed with standard chemotherapy agents. The effect of the drug was dose-dependent, so the more drug the researchers added to the cells, the less the cells proliferated.

The researchers then studied PD173074 in mice using two different types of human small cell lung cancer tumours. They tested the drug on its own and alongside the standard chemotherapy agent cisplatin, which is frequently used to treat patients with the disease. In the first mouse model, PD173074 given on its own killed off tumours in 50 per cent of the mice and these mice remained disease-free for at least one year. In the second mouse model, both PD173074 and cisplatin alone slowed down tumour growth. When the drugs were combined, they slowed down tumour growth significantly faster than either drug on its own.

The researchers also used PET scanning to show that the drug reduced DNA synthesis in the tumours, which indicates that the drug was preventing cell proliferation. The researchers also found that the rate of cell death, or apoptosis, in the tumours increased after the drug was given to the mice.

PD173074 was developed in 1998 to stop blood vessels from forming around tumours. The research is the first to show this drug has a therapeutic effect on tumours in mice.

The research was funded by the Cancer Treatment and Research Trust, Cancer Research UK and the UK Department of Health.

Source: Lucy Goodchild

Imperial College London

Novavax, Inc. (Nasdaq: NVAX) announced final selection of a Respiratory Syncytial Virus (RSV) vaccine candidate that will be advanced into additional preclinical studies to support an Investigational New Drug (IND) application. As previously announced, Novavax has been evaluating a number of RSV vaccine candidates, all of which have successfully induced antibody responses in mice. Novavax scientists have now engineered a new vaccine candidate which has been shown to protect mice against RSV disease and can be produced at sufficient yields to allow commercial manufacture. This new candidate is directed against a protein on the surface of the virus, the “F” or “fusion” protein, which is the protein that the virus uses to infect and fuse with cells in the respiratory tract and cause disease.

The new RSV-F vaccine candidate consists of novel three-dimensional particles containing the F protein. The structure of the F protein in these particles is identical to the configuration in which it exists on the surface of the native virus. The particle nature of the vaccine holds the promise for inducing a broad set of immune responses including antibody and cell mediated immune responses to prevent infection of the respiratory tract and attack respiratory cells that may already be infected with RSV.

The first preclinical study of this new vaccine candidate in mice showed that it induced production of antibodies that neutralized live RSV. In addition, the vaccine protected mice against replication of RSV in the lungs. The study included groups of mice that received two injections of RSV-F vaccine at doses of 1, 10, or 30 micrograms with and without adjuvant. The study showed that the RSV-F vaccine induced neutralizing antibody responses at all doses evaluated. The highest titers were observed with vaccine formulations that contained an aluminum-based adjuvant. Following vaccination, mice were exposed to live RSV through the nose. Even without adjuvant, the lowest dose (1.0 mcg) of RSV-F vaccine prevented RSV infection in the lungs of these mice. However, protection from RSV infection was not observed in unvaccinated mice. Based on these favorable pre-clinical data obtained with this RSV-F vaccine candidate and the ability to produce it at commercial yields, the Company has selected it for advanced preclinical development.

Today, the only therapy against RSV disease is a monoclonal F antibody. The antibody reduces RSV-related hospitalizations in infants and young children at high risk of severe disease. However, several injections are required and the lifespan of the antibody in the body has a limited duration. Therefore, a vaccine that induces long lasting protection against RSV-F would be highly desired by healthcare providers. There is currently no approved vaccine for the prevention of RSV and the market potential for such a vaccine could exceed $1 billion annually.

Dr. Penny Heaton, Chief Medical Officer and Vice President of Development at Novavax, stated: “A vaccine against the RSV-F protein is an ideal candidate to progress into advanced preclinical testing. Studies of the monoclonal RSV-F antibody show it protects against hospitalizations for severe RSV disease, suggesting that a vaccine which induces neutralizing antibody against RSV-F has the potential to be a powerful weapon against this disease.”

ABOUT RESPIRATORY SYNCYTIAL VIRUS

RSV is the most commonly identified cause of lower respiratory tract illnesses in infants and young children. Repeated infections occur throughout life causing moderate to severe cold-like symptoms. More severe lower respiratory tract disease is also seen in elderly adults over age 65 years similar to the severe illness witnessed in children. It is estimated that RSV infects more than 8.5 million adults annually, including the elderly over age 65 years. This virus is responsible for approximately 900,000 hospitalizations annually in the United States and major European countries. In the United States alone, RSV leads to 177,500 hospitalizations in high risk adults resulting in annual medicals costs exceeding $1 billion.

ABOUT NOVAVAX

Novavax, Inc. (Nasdaq: NVAX) is a clinical-stage biotechnology company creating novel vaccines, including H1N1, to address a broad range of infectious diseases worldwide using advanced proprietary virus-like-particle (VLP) technology. The company produces these VLP-based, potent, recombinant vaccines utilizing new and efficient manufacturing approaches.

Forward Looking Statement

Statements herein relating to future development results and performance, conditions or strategies and other matters, including expectations regarding product and clinical developments, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. Novavax cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks relating to the early stage of Novavax’s product candidates under development; current results may not be predictive of future results; further testing is required before an IND may be filed with the FDA and human clinical trials can begin; uncertainties relating to clinical trials; results in human clinical trials may not be consistent with animal study results; dependence on the efforts of third parties; competition for clinical resources and patient enrollment from drug candidates in development by other companies with greater resources and visibility; and risks that we may lack the financial resources and access to capital to fund our operations including further preclinical work and clinical trials.

Source: Novavax, Inc